Metastatic Consequences of Immune Escape from NK Cell Cytotoxicity by Human Breast Cancer Stem Cells

被引：171

作者：

Wang, Bin ^{[1
,2
,3
]}

Wang, Qiang ^{[1
,2
,3
]}

Wang, Zhe ^{[1
,2
,3
]}

Jiang, Jun ^{[4
]}

Yu, Shi-Cang ^{[1
,2
,3
]}

Ping, Yi-Fang ^{[1
,2
,3
]}

Yang, Jing ^{[1
,2
,3
]}

Xu, Sen-Lin ^{[1
,2
,3
]}

Ye, Xian-Zong ^{[1
,2
,3
]}

Xu, Chuan ^{[1
,2
,3
]}

Yang, Lang ^{[1
,2
,3
]}

Qian, Cheng ^{[1
,2
,3
]}

Wang, Ji Ming ^{[5
]}

Cui, You-Hong ^{[1
,2
,3
]}

Zhang, Xia ^{[1
,2
,3
]}

Bian, Xiu-Wu ^{[1
,2
,3
]}

机构：

[1] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China

[3] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing, Peoples R China

[4] Third Mil Med Univ, Southwest Hosp, Breast Surg Ctr, Chongqing 400038, Peoples R China

[5] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA

来源：

CANCER RESEARCH | 2014年 / 74卷 / 20期

基金：

中国国家自然科学基金;

关键词：

NATURAL-KILLER-CELLS; TUMOR-CELLS; MESENCHYMAL TRANSITION; INITIATING CELLS; IN-VITRO; RECOGNITION; EXPRESSION; RESPONSES; MICRORNA; RECEPTOR;

D O I：

10.1158/0008-5472.CAN-13-2563

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation-inducing agent, all-trans retinoic acid, restored the miR20a-MICA/MICB axis and sensitized BCSC to NK cell-mediated killing, thereby reducing immune escape-associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a-MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer. (C) 2014 AACR.

引用

页码：5746 / 5757

页数：12